1. Field of the Invention
This invention relates to inverse magnetic particle processing, more particularly, reusable sheaths for magnets.
2. Discussion of the Art
The ThermoFisher Kingfisher™ magnetic particle separation system performs in vitro diagnostic assays. The KingFisher™ mL magnetic particle processor is described in detail in KingFisher™ mL User manual, Revision No. 1.0, February 2002, Catalog No. 1508260, incorporated herein by reference. The KingFisher™ magnetic particle processor is described in detail in KingFisher™ Micro-well User Manual, Revision No. 1.0, 1999-04-09, Catalog No. 1507730, incorporated herein by reference. The KingFisher™ magnetic particle processor is designed for automated transfer and processing of magnetic particles in volumes of liquids suitable for micro-wells. The KingFisher™ mL magnetic particle processor employs greater volumes of liquids than does the KingFisher™ magnetic particle processor. Regardless of which of the aforementioned KingFisher™ instrument is being used, the operating principle employed is inverse magnetic particle processing technology, commonly referred to as MPP. According to inverse magnetic particle processing technology, magnetic particles are transferred with the aid of magnetic rods covered with disposable, specially designed plastic tip combs.
Referring now to FIGS. 1 and 2, a KingFisher™ mL magnetic particle processor 10 can be used for automated transfer and processing of magnetic particles in tubes of a tube strip. In the description that follows, the tubes of the tube embodiment will be used to illustrate the concentrating technique. The principle of the KingFisher™ mL magnetic particle processor 10 is based on the use of (a) magnetic rods 12a, 12b, 12c, 12d, and 12e that can be covered with a disposable tip comb 14 and (b) tube strips 16. A tip comb 14 comprises a strip of non-magnetic material that joins a plurality of sheaths 14a, 14b, 14c, 14d, and 14e made of non-magnetic material for covering magnetic rods. A tube strip 16 is a plurality of tubes 16a, 16b, 16c, 16d, and 16e arranged in a row. The KingFisher™ mL magnetic particle processor 10 is capable of functioning without any aspiration and/or dispensing devices. The KingFisher™ mL magnetic particle processor 10 is designed for a maximum of fifteen (15) tube strips 16, which are compatible with the tip comb 14. The tube strip(s) 16 is (are) maintained stationary and the only movable assembly is a processing head 18 along with the tip combs 14 and magnetic rods 12a, 12b, 12c, 12d, and 12e associated therewith. The processing head 18 comprises two vertically moving platforms 20, 22. One platform 20 is needed for the magnetic rods 12a, 12b, 12c, 12d, and 12e, and the other platform 22 is needed for the tip combs 14. A tray 24 contains 15 separate tube strips 16 and a single sample processing typically uses one tube strip 16 containing five tubes 16a, 16b, 16c, 16d, and 16e. One tip comb 14 containing five sheaths 14a, 14b, 14c, 14d, and 14e is used for processing five samples at one time. In FIG. 2, only one magnetic rod 12a and only one sheath 14a are numbered. Magnetic rods 12b, 12c, 12d, and 12e and sheaths 14b, 14c, 14d, and 14e are not numbered in FIG. 2.
Before starting the magnetic particle processing via a keypad (not shown) and a display (not shown), the samples and reagents are dispensed into the tubes 16a, 16b, 16c, 16d, and 16e and the tip comb(s) 14 is (are) loaded into its (their) slot(s). The tube strip(s) 16 is (are) placed into the removable tray in the correct position and the tray is pushed into the end position. During the operation, the front and top lids can be closed or open. Closed lids protect the processing against environmental contamination.
Rather than moving the liquids from one tube to another tube, the magnetic particles are moved from one tube 16a to another tube 16b, at least one tube containing specific reagent(s). This principle stands in contrast to the external magnet method, i.e., the type of separation used in the apparatus shown in U.S. Pat. Nos. 5,795,784 and 5,856,194.
Working with magnetic particles can be divided into five separate process steps:                Collecting particles: In this step, magnetic particles are collected from the well or tube specified.        Binding particles: In this step, material is collected onto the magnetic particles from the reagent in a specific well or tube.        Mixing particles: In this step, the reagent and particles (if inserted), are mixed with the plastic sheath in a specific well or tube.        Releasing particles: In this step, the collected material is released from the surfaces of the magnetic particles into a specific well or tube.        Washing particles: In this step, the magnetic particles are washed in a specific well or tube.        
FIGS. 3A, 3B, 3C, 3D, 3E, and 3F illustrate the sequence of steps employed in collecting, transferring, and releasing magnetic particles from tubes in a KingFisher™ mL magnetic particle processor. During the collection of the magnetic particles, each magnetic rod 12a is substantially completely enclosed in a sheath 14a. See FIG. 3A. Only magnetic rod 12a and only sheath 14a are shown, but four additional magnetic rods 12b, 12c, 12d, and 12e and four additional sheaths 14b, 14c, 14d, and 14e are also employed. The magnetic rod(s) 12a together with the tip comb(s) 14 move slowly up and down in the tube(s) 16a and the magnetic particles “P” are collected onto the wall(s) of the sheath(s) 14a. See FIG. 3B. Only tube 16a is shown, but four additional tubes, aligned with the four additional sheaths 14b, 14c, 14d, and 14e, are also employed. The magnetic rod(s) 12a together with the tip comb(s) 14, having collected the magnetic particles “P”, can be lifted out of the tube(s) 16a and transferred into the next tube(s) 16b. See FIG. 3C. After collection of the magnetic particles “P”, the magnetic rod(s) 12a together with the tip comb(s) 14 are lifted from the tube(s) 16b, the magnetic rod(s) 12a are lifted off and the tip comb(s) 14 is (are) lowered into the tube(s) 16b containing a reagent. See, for example, FIGS. 3D and 3E. Magnetic particles “P” are released by moving the tip comb(s) 14 up and down several times at considerably high speed until all the particles have been mixed with the substance in tube(s) 16b to carry out the next reaction. See FIG. 3F. Washing the magnetic particles “P” is a frequent and an important phase of the process. Washing is a combination of the release and collection processes in a tube(s) filled with washing solution. To maximize washing efficiency, the magnetic rod(s) 12a together with the tip comb(s) 14 are designed to have minimized liquid-carrying properties. To keep the magnetic particle suspension evenly mixed in long-running reactions, the tip comb(s) 14 can be moved up and down from time to time. The volume of the first tube can be larger than the volume of the next tube for concentration purposes. For additional discussion relating to the KingFisher™ mL magnetic particle processor, see U.S. Patent Application Publication No. US-2009-0181359-A1, published Jul. 16, 2009, incorporated herein by reference.
The ThermoFisher KingFisher™ system utilizes a linear array of magnets along with a linear array of sheaths, i.e., the sheaths of the tip combs. These tip combs are disposed of after each use.
U.S. Pat. No. 5,183,638 discloses an immunity analysis apparatus for use with magnetic particles in which a sample is transferred to a reaction vessel and the reaction vessel is conveyed past several devices for adding and agitating a magnetic particle solution, adding a stroma solution, absorbing the particles to an inner wall of the reaction vessels to remove the reaction solution, adding an enzyme labeling antibody solution, absorbing the particle on an inner wall a second time to remove the resulting solution, adding a stop solution, measuring the result, and cleaning the reaction vessels for reuse. The device additionally has a structure for agitating the magnetic particle reagent solution containers and moving a pipet arm independent of an L-shaped agitating rod arm during a portion of its movement top supply the reaction vessels with the magnetic particle solution.
U.S. Pat. No. 6,193,892 discloses a magnetic particle separation assembly and method for separating a magnetically responsive complex from a non-magnetic test media in which the magnetically responsive complex is suspended. The assembly comprises an invertible rack for holding specimen containers and a magnetic support member for supporting the rack. The magnetic support member has a base and a planar member bisecting the base and extending upwardly therefrom. The planar vertical member has a plurality of magnets embedded therein. The magnets are disposed in a substantially horizontal orientation parallel to the base and spaced from the base. The invertible rack has a slot therethrough dimensioned to accept the planar vertical member of the magnetic support member.
U.S. Pat. No. 6,312,910 discloses a multistage electromagnetic separator is designed to separate magnetically susceptible materials suspended in fluids. The apparatus includes an upper plate and a lower plate set to a fill position and the fluid samples are filled into upper and lower cuvettes. A translating electromagnet energizes to a programmed current level and translates from the bottom of the lower cuvette to the interface of the plates. The translating electromagnet is de-energized, and a holding electromagnet is energized to a programmed current level pulling particles within a specified mobility range into the top of the captured upper collection cuvette. The holding electromagnet is de-energized leaving the permanent holding magnet to keep the collected sample particles in the top cuvette while the upper plate rotates thereby capturing the sample of the collected particles. The process can be preprogrammed to vary or remain the same for a plurality of captured cuvettes.
U.S. Pat. No. 6,325,927 discloses a magnetic separator apparatus having a configuration of barium ceramic magnets impregnated into polypropylene bars interspersed onto a conveyor belt which passes through an aqueous solution containing unwanted magnetic particulate. A plurality of spaced-apart magnet pairs embedded in each polypropylene bar are configured to provide maximum field penetration and holding strength of the magnets. Particulate attracted to the plurality of magnet pairs are scraped from the conveyor belt into a collection drawer.
U.S. Pat. No. 6,579,453 discloses an apparatus for separating magnetic particles in suspension in a liquid contained in a reaction vessel of the type used in an automatic apparatus for processing biological samples. The apparatus comprises a rotatable carrier holding an array of magnet elements positioned on the carrier at different distances from the rotation axis of the carrier and at different azimuth angles. The carrier and the array of magnet elements can be positioned at a plurality of predetermined angular positions and heights.
None of the foregoing references disclose an inverse magnetic particle processing apparatus capable of reusing sheaths 14a, 14b, 14c, 14d, and 14e. Accordingly, it is desired to develop an apparatus and method for transferring reacting particles from one reaction vessel to another while preventing contamination and at the same time reducing, or even eliminating, the quantity of solid biohazardous material that is generated during the operation of the apparatus and method.